Cystrin 3mg Tablets, Cystrin 5mg Tablets

1. Name Of The Medicinal Product

Cystrin 3mg Tablets

Cystrin 5mg Tablets

2. Qualitative And Quantitative Composition

Oxybutynin hydrochloride 3.00mg

Oxybutynin hydrochloride 5.00mg

3. Pharmaceutical Form

Tablet

4. Clinical Particulars

4.1 Therapeutic Indications

Cystrin is indicated for urinary incontinence, urgency and frequency in unstable bladder conditions due either to idiopathic detrusor instability or neurogenic bladder disorders (detrusor hyperreflexia) in conditions such as spina bifida and multiple sclerosis.

In addition, for children over 5 years of age, oxybutynin may be used in nocturnal enuresis in conjunction with non-drug therapy where this alone, or in conjunction with other drug treatment, has failed.

4.2 Posology And Method Of Administration

Children under 5 years of age: Not recommended

Children over 5 years of age:

Neurogenic bladder disorders: The usual dose is 5mg twice a day. This may be increased to a maximum of 5mg three times a day to obtain a clinical response provided that the side effects are tolerated.

Nocturnal enuresis: The usual dose is 5mg two or three times a day. The last dose should be given before bedtime.

In children the maintenance dose may be achieved by upward titration from an initial dose of 3mg twice daily.

Adults: The usual dose is 5mg two or three times a day. This may be increased to a maximum dosage of 5mg four times a day (20mg) to obtain a satisfactory clinical response provided that the side effects are tolerated.

Elderly: The elimination half-life may be increased in some elderly patients, therefore, dosage should be individually titrated commencing at 3mg twice a day. The final dosage will depend on response and tolerance to side-effects. As with other anticholinergic drugs caution should be observed in frail and elderly patients.

4.3 Contraindications

Hypersensitivity to oxybutynin or any component.

Myasthenia gravis.

Narrow-angle glaucoma or shallow anterior chamber.

Gastrointestinal obstruction including paralytic ileus, intestinal atony.

Patients with toxic megacolon, severe ulcerative colitis.

Patients with bladder outflow obstruction where urinary retention may be precipitated.

4.4 Special Warnings And Precautions For Use

Oxybutynin should be used with caution in the frail elderly and children who may be more sensitive to the effects of the product and in patients with autonomic neuropathy, hepatic or renal impairment and severe gastro-intestinal motility disorders (also see section 4.3).

Oxybutynin may aggravate the symptoms of hyperthyroidism, congestive heart failure, coronary heart disease, cardiac arrhythmia, tachycardia, hypertension and prostatic hypertrophy.

Oxybutynin can cause decreased sweating; in high environmental temperatures this can lead to heat prostration.

The use of oxybutynin in children under 5 years of age is not recommended; it has not been established whether oxybutynin can be safely used in this age group.

Special care should be taken in patients with hiatus hernia associated with reflux oesophagitis, as anticholinergic drugs can aggravate this condition.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Care should be taken if other anticholinergic agents are administered together with Cystrin, as potentiation of anticholinergic effects could occur.

Occasional cases of interaction between anticholinergics and clozapine, phenothiazines, amantidine, butyrophenones, L-dopa, digitalis and tricyclic antidepressants have been reported and care should be taken if Cystrin is administered concurrently with such drugs.

By reducing gastric motility, oxybutynin may affect absorption of other drugs.

4.6 Pregnancy And Lactation

Pregnancy

There is no experience of the use of oxybutynin during pregnancy in humans, however, in foetal toxicity and fertility studies in animals, effects were seen on reproductive processes at dosages associated with maternal toxicity. Cystrin should, therefore, only be prescribed during pregnancy if considered essential.

Lactation

Small amounts of oxybutynin have been found in mother's milk of lactating animals. Breast feeding while using oxybutynin is therefore not recommended.

4.7 Effects On Ability To Drive And Use Machines

As Cystrin may produce drowsiness or blurred vision, the patient should be cautioned regarding activities requiring mental alertness such as driving, operating machinery or performing hazardous work while taking this drug.

4.8 Undesirable Effects

Gastro-intestinal disorders

Nausea, diarrhoea, constipation, dry mouth, abdominal discomfort, anorexia, vomiting, gastroesophageal reflux.

CNS and psychiatric disorders

Agitation, headache, dizziness, drowsiness, disorientation, hallucinations, nightmares, convulsions.

Cardiovascular disorders

Tachycardia, cardiac arrythmia.

Vision disorders

Blurred vision, mydriasis, intraocular hypertension, onset of narrow-angle glaucoma, dry eyes.

Renal and urinary disorders

Urinary retention, difficulty in micturition.

Skin and appendages

Facial flushing which may be more marked in children, dry skin, allergic reactions such as rash, urticaria, angioedema, photosensitivity.

4.9 Overdose

The symptoms of overdosage with oxybutynin progress from an intensification of the usual side-effects of CNS disturbances (from restlessness and excitement to psychotic behaviour), circulatory changes (flushing, fall in blood pressure, circulatory failure etc), respiratory failure, paralysis and coma.

Measures to be taken are:

(1) immediate gastric lavage and

(2) physostigmine by slow intravenous injection

Adults: 0.5 to 2.0 mg of physostigmine by slow intravenous administration. Repeat after 5 minutes, if necessary up to a maximum total dose of 5mg

Children: 30 micrograms/kg of physostigmine by slow intravenous administration. Repeat after 5 minutes, if necessary up to a maximum total dose of 2mg.

Fever should be treated symptomatically with tepid sponging or ice packs.

In pronounced restlessness or excitation, diazepam 10mg may be given by intravenous injection. Tachycardia may be treated with intravenous propanolol and urinary retention managed by bladder catheterization.

In the event of progression of the curare-like effect to paralysis of the respiratory muscles, mechanical ventilation will be required.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Oxybutynin hydrochloride is an anticholinergic agent which also exerts a direct antispasmodic effect on smooth muscle. It inhibits bladder contraction and relieves spasm induced by various stimuli; it increases bladder volume, diminishes the frequency of contractions and delays the desire to void in the disturbance of neurogenic bladder. The relaxation of smooth muscle results from the papaverin like effect of the antagonism of the processes distal to the neuromuscular junction in addition to the anticholinergic blocking action of the muscarinic type receptors. In addition oxybutynin hydrochloride has local anaesthetic properties.

5.2 Pharmacokinetic Properties

Pharmacodynamic reports show oxybutynin to be rapidly absorbed from the gastrointestinal tract following oral administration with maximum plasma concentrations reached in less than 1 hour subsequently falling bioexponentially with a half-life of between 2 and 3 hours. Maximum effect can be seen within 3-4 hours with some effect still evident after 10 hours.

Repeated oral administration achieved steady state after eight days. Oxybutynin does not appear to accumulate in elderly patients and the pharmacokinetics are similar to those in other adults. Some excretion via the biliary system has been observed in the rabbit and partial first-pass metabolism occurs, the metabolites also appearing to have antimuscarinic properties. The main elimination route is via the kidneys with only 0.3-0.4% of unchanged drug appearing in the urine of the rat after 24 hours and 1% appearing in the urine of the dog after 48 hours. In rats and dogs therefore, oxybutynin appears to be almost completely absorbed.

5.3 Preclinical Safety Data

No additional data available.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose anhydrous, microcrystalline cellulose, calcium stearate, indigo carmine aluminium lake (E132).

6.2 Incompatibilities

None known

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Store below 30°C.

6.5 Nature And Contents Of Container

Cystrin 3mg: 56 tablets in aluminium/PVC blister strips which are contained within a printed Cardboard carton.

Cystrin 5mg: 84 tablets in aluminium/PVC blister strips which are contained within a printed cardboard carton.

6.6 Special Precautions For Disposal And Other Handling

No relevance.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

8. Marketing Authorisation Number(S)

Cystrin 3mg: PL 04425/0192

Cystrin 5mg: PL 04425/0193

9. Date Of First Authorisation/Renewal Of The Authorisation

25th March 2009

10. Date Of Revision Of The Text

1 October 2009

Legal Category: POM